Virtual Screening For Anti-Angiogenesis Flavonoids From Sophora Flavescens Ait

Angiogenesis is a dynamic process involving multiple steps.And it is known that about 70 diseases are associated with neovascular disorders.Sophora flavescens is also named KuShen(KS)in Chinese.In the preliminary literature investigation,the results showed that the flavonoids from Sophora flavescens(KS-SFs)had the effect of inhibiting angiogenesis,but its pharmacological basis and mechanism of action were not clear.As we know that the technique of molecular docking can be used to find and explore new lead compounds.In this study,molecular docking technique was used to screen the active constituents for angiogenesis from KS-SFs,as well as validating the results of virtual screening by biological test with separation of chemical composition in traditional Chinese medicine.We collected 142 compounds of KS-SFs as the ligand database,and 9 targets which related to angiogenesis as the receptor database(such as VEGF-a,KDR and FLT1).And using the LibDock module in Discovery Studio 2.5(DS2.5)to complete molecular docking.Taking the approved drugs of each target from DrugBank as references,and setting the minimum score among each target's approved drugs as threshold.A total of 42 compounds were screened out which being higher than threshold and in the top 10%.Furtherly,the mechanism of action about anti-angiogenesis was preliminarily revealed.Referring to the results of virtual screening,we isolated the compounds from KS.And then one flavonoid compound named Kuraridin(16)was selected for the biological test in zebrafish about anti-angiogenesis.The result showed that Kuraridin(16)has the effect of inhibiting the angiogenesis in zebrafish.Meanwhile,the result further demonstrate the reliability of the virtual screening method.In this study,firstly,we established a virtual screening method for anti-angiogenesis flavonoids from KS,and preliminarily discussed the mechanism of inhibiting angiogenesis.Secondly,we demonstrated the reliability of this method by biological test in zebrafish.This study can be used to guide further studies on the separation and pharmacodynamics of KS-SFs and provide a reference for the development of angiogenesis inhibitors.